gemcitabine plus nab-paclitaxel is an active regimen in….ppt

Gemcitabine Plus nab-Paclitaxel Is an Active Regimen inPatients With Advanced Pancreatic Cancer (PDA) A Phase I/II TrialDaniel D. Von Hoff, Ramesh K. Ramanathan, Mitesh J. Borad, Daniel Laheru, Lon S. Smith, Tina E. Wood, Ronald L. Korn, Neil Desai, Vuong Trieu, Jose L. Iglesias, Hui Zhang, Patrick Soon-Shiong, Tao Shi, . Rajeshkumar, Anirban Maitra, and Manuel HidalgoJ Clin Oncol 2011; online Oct 3rd Objectives?Identify the MTD of 1st-line Gemcitabine plus nab-paclitaxel?Provide efficacy and toxicity data–PET scan response –SPARC–CA19-9 levels in relation to efficacy–Subsequent preclinical studies investigated the changes involving the pancreatic stroma and drug / Eligibility criteria?18 years ?Histologically or cytologically confirmed metastatic PDA ?Measurable disease by CT-scan (RECIST )?No previous treatment for metastatic disease?Prior adjuvant treatment with fluorouracil or gemcitabine administered as a radiation sensitizer during and up to 4 weeks after radiation therapy was allowed. If a patient received adjuvant therapy, tumor recurrence must have occurred 6 months after the last treatment. ?ECOG PS = 0 or 1 ?Adequate hematologic, hepatic, and renal functionStudy Design?Phase I –Identify MTD and DLT –Standard 3 + 3 dose-escalation?DLTs treatment-related toxicities during cycle 1 per NCI-CTCAE –Any grade 4 hematologic toxicity–Grade 3 thrombocytopenia with hemorrhage;–Grade 3 nausea, vomiting, or diarrhea despite prophylaxis–Any grade3 treatment-related nonhematologic toxicity, excluding alopecia and fatigue.–Dose escalation stopped when 1 of 3 pts had DLTs, and the dose below was declared the MTD–Patients continued treatment until PD or eptable toxicityDose LevelsTreatment Dose Finding150 mg/m2 . Week 1181522DaysWeek 2Week 3Week 428125 mg/m2 . 100 mg/m2 . nabPaclitaxelGemcitabine 1000 mg/m2 . Assessments?CT-scans baseline and every 4 weeks on day 1 of each cycle (RECIST v1)–An initial response (CR or PR) had to be